Monitoring for mitral valve regurgitation

ABSTRACT

Implantable systems, and methods for use therein, for monitoring for mitral valve regurgitation (MR) are provided. An electrogram (EGM) signal and a corresponding pressure signal are obtained, where the EGM signal is representative of electrical functioning of the patient&#39;s heart during a plurality of cardiac cycles, and the corresponding pressure signal is representative of pressure within the left atrium the patient&#39;s heart during the cardiac cycles. Windows of the pressure signal are defined, based on events detected in the EGM signal, and measurements from the windows are used to monitor for MR.

RELATED APPLICATION

The present application relates to commonly invented and commonlyassigned U.S. patent application Ser. No. 11/537,302, entitled“Estimating Mean Left Atrial Pressure,” which was filed the same day asthe present application, and which is incorporated herein by reference.

FIELD OF THE INVENTION

Embodiments of present invention relate to monitoring for mitral valveregurgitation (MR).

BACKGROUND

Heart failure is a condition in which a patient's heart works lessefficiently than it should, resulting in the heart failing to supply thebody sufficiently with the oxygen rich blood it requires, either atexercise or at rest. Congestive heart failure (CHF) is heart failureaccompanied by a build-up of fluid pressure in the pulmonary bloodvessels that perfuse the lungs. Transudation of fluid from the pulmonaryveins into the pulmonary interstitial spaces, and eventually into thealveolar air spaces, is called pulmonary edema, and can cause shortnessof breath, hypoxia, acidosis, respiratory arrest, and even death.

Chronic diseases such as CHF require close medical management to reducemorbidity and mortality. Because the disease status evolves with time,frequent physician follow-up examinations are typically necessary. Atfollow-up, the physician may make adjustments to the drug regimen inorder to optimize therapy. This conventional approach of periodicfollow-up is unsatisfactory for some diseases, such as CHF, in whichacute, life-threatening exacerbations can develop between physicianfollow-up examinations. It is well know among clinicians that if adeveloping exacerbation is recognized early, it can be more easily andinexpensively terminated, typically with a modest increase in oraldiuretic. However, if it develops beyond the initial phase, an acuteheart failure exacerbation becomes difficult to control and terminate.Hospitalization in an intensive care unit is often required. It isduring an acute exacerbation of heart failure that many patients succumbto the disease.

It is often difficult for patients to subjectively recognize adeveloping exacerbation, despite the presence of numerous physical signsthat would allow a physician to readily detect it. Furthermore, sinceexacerbations typically develop over hours to days, even frequentlyscheduled routine follow-up with a physician cannot effectively detectmost developing exacerbations. It is therefore desirable to have asystem that allows for routine, frequent monitoring of patients so thatan exacerbation can be recognized early in its course. With the patientand/or physician thus notified by the monitoring system of the need formedical intervention, a developing exacerbation can more easily andinexpensively be terminated early in its course.

Mitral valve regurgitation (MR) is a condition in which the mitral valvedoesn't close tightly, which allows blood to flow backward in apatient's heart. When the mitral valve doesn't function properly, bloodcan't move through the heart or to the rest of the patient's body asefficiently. The condition can leave a patient fatigued and short ofbreath. As many as one in five people over age 55 have some degree ofMR. Treatment of MR depends on the severity and progression of thecondition and signs and symptoms. A patient may need heart surgery torepair or replace the valve. Left unchecked, severe MR can lead to CHFor serious heart rhythm irregularities (i.e., arrhythmias). MR is alsocalled mitral insufficiency, mitral incompetence or simply mitralregurgitation.

Accordingly, it would be advantageous to provide implantable cardiacdevices that can obtain information about a patient's heart failureprogression and information about occurrences of MR. More generally, itis desirable to provide implantable cardiac devices that can obtaindisease progression information.

SUMMARY

Certain embodiments of the present invention relate to implantablesystems, and method for use therein, for monitoring a patient's heartfor MR. In accordance with specific embodiments of the presentinvention, an EGM signal and a corresponding pressure signal areobtained, where the EGM signal is representative of electricalfunctioning of the patient's heart during a plurality of cardiac cycles,and the corresponding pressure signal is representative of pressurewithin the left atrium of the patient's heart during the cardiac cycles.In accordance with specific embodiments, for each of a plurality ofcardiac cycles represented in the EGM and pressure signals, there is adetermination of a maximum peak within a first window of the pressuresignal, and a determination of a maximum peak within a second window ofthe pressure signal. The maximum peak detected within one or more firstwindow is compared to the maximum peak detected within one or moresecond window. MR is monitored for based on results of the comparison.

In accordance with specific embodiments, a start of the first window isdefined relative to an event detected in the EGM signal, and a length ofthe first window is defined to include at least one of an a-wave and ac-wave, but not a v-wave, of the cardiac cycle represented in thepressure signal. In accordance with certain embodiments, a start of thesecond window is defined relative to an event detected in the EGM signalor relative to the first window, and a length of the second window isdefined to include the v-wave of the cardiac cycle represented in thepressure signal.

In accordance with other embodiments, for each of a plurality of cardiaccycles represented in the EGM and pressure signals, there is adetermination of a maximum peak within a first window of the pressuresignal, there is a determination of an average of a first window of thepressure signal, and a determination of an average of a second window ofthe pressure signal. One or more average determined for a first windowis compared to one or more average determined for a second window, andMR is monitored based on results of the comparison.

This description is not intended to be a complete description of, orlimit the scope of, the invention. Additional and alternative features,aspects, and objects of the invention can be obtained from a review ofthe specification, the figures, and the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a simplified diagram illustrating an exemplary implantabledevice in electrical communication with a patient's heart by means ofmultiple leads suitable for delivering multi-chamber stimulation andpacing therapy.

FIG. 1B is useful for describing how pressure sensors can be implantedwithin a patient's heart and connected by leads to the implantabledevice of FIG. 1A.

FIG. 2 is a functional block diagram of the exemplary implantabledevice, which can provide cardioversion, defibrillation, and pacingstimulation in four chambers of a heart, and can estimate mean LAPand/or detect MR, in accordance with embodiments of the presentinvention.

FIG. 3A illustrates a portion of an exemplary EGM signal.

FIG. 3B illustrates an exemplary pressure signal representative ofpressure within the left atrium a patient's heart, where the pressuresignal corresponds to the EGM signal of FIG. 3A.

FIG. 3C illustrates an exemplary pressure signal representative ofpressure within the left atrium a patient's heart, when the patient isexperiencing MR.

FIG. 4 is a high level flow diagram that is useful for describing howmeasures of mean left atrial pressure (LAP) can be estimated, inaccordance with embodiments of the present invention.

FIG. 5 is a high level flow diagram that is useful for describing how tomonitor for MR, in accordance with embodiments of the present invention.

FIG. 6 is a high level flow diagram that is useful for describing how tomonitor for MR, in accordance with alternative embodiments of thepresent invention.

FIG. 7 is an exemplary graph of MR burden versus time that can beproduced using embodiments of the present invention.

In accordance with common practice the various features illustrated inthe drawings may not be drawn to scale. Accordingly, the dimensions ofthe various features may be arbitrarily expanded or reduced for clarity.In addition, some of the drawings may be simplified for clarity. Thus,the drawings may not depict all of the components of a given apparatusor method. Finally, like reference numerals denote like featuresthroughout the specification and figures.

DETAILED DESCRIPTION

The following detailed description of the present invention refers tothe accompanying drawings that illustrate exemplary embodimentsconsistent with this invention. Other embodiments are possible, andmodifications may be made to the embodiments within the spirit and scopeof the present invention. Therefore, the following detailed descriptionis not meant to limit the invention. Rather, the scope of the inventionis defined by the appended claims.

It would be apparent to one of skill in the art that the presentinvention, as described below, may be implemented in many differentembodiments of hardware, software, firmware, and/or the entitiesillustrated in the figures. Any actual software and/or hardwaredescribed herein is not limiting of the present invention. Thus, theoperation and behavior of the present invention will be described withthe understanding that modifications and variations of the embodimentsare possible, given the level of detail presented herein.

It is believed that chronic monitoring of the pressures within thechambers of the heart will be important in future cardiac pulsegenerator applications. To monitor congestive heart failure (CHF)status, clinicians ideally would like to know left ventricularend-diastolic pressure (LVEDP). However, it is rarely possible todirectly measure LVEDP because of the invasiveness required of atransducer capable of making such a measurement. An alternative is tomeasure left atrial pressure (LAP) at a time when the pressure in theleft atrium and left ventricle is the same, namely at the end of anatrial contraction, when the mitral valve (located between the left andright atrium) is still open. This is the end of ventricular diastole.The most clinically-relevant time then to report LAP is in thisinterval. Accordingly, there is a desire to provide relatively accurateand efficient systems and methods for measuring LAP. Such LAPmeasurements can then be used as an estimate or surrogate for LVEDP, incertain embodiments of the present invention.

Before describing embodiments of the invention in additional detail, itis helpful to first describe an example environment in which embodimentsof the invention may be implemented.

Embodiments of the present invention are particularly useful in theenvironment of an implantable cardiac device that may monitor electricalactivity of a heart and deliver appropriate electrical therapy,including for example, pacing pulses, cardioverting and defibrillatorpulses, and/or drug therapy, as required. Implantable cardiac devicesinclude, for example, pacemakers, cardioverters, defibrillators,implantable cardioverter defibrillators, and the like. The term“implantable cardiac device” or simply “ICD” is used herein to refer toany implantable cardiac device, even those that don't deliver electricalstimulation (e.g., the implantable device may simply be a monitor thatrecords data). FIGS. 1A and 2, discussed below, illustrate such anenvironment in which embodiments of the present invention can be used.FIG. 1B, which is useful for describing how pressure sensors can beimplanted within a patient's heart and connected by leads to theimplantable device of FIG. 1A, is also discussed below.

Referring first to FIG. 1A, an exemplary implantable device 100 is shownas being in electrical communication with a patient's heart 102 by wayof three leads 104, 106, and 108, suitable for delivering multi-chamberstimulation and shock therapy. To sense atrial cardiac signals and toprovide right atrial chamber stimulation therapy, implantable device 100is coupled to an implantable right atrial lead 104 having at least anatrial tip electrode 120, which typically is implanted in the patient'sright atrial appendage or septum. FIG. 1A shows the right atrial lead104 also as having an optional atrial ring electrode 121.

To sense left atrial and ventricular cardiac signals and to provide leftchamber pacing therapy, implantable device 100 is coupled to a coronarysinus lead 106 designed for placement in the coronary sinus region viathe coronary sinus for positioning a distal electrode adjacent to theleft ventricle and/or additional electrode(s) adjacent to the leftatrium. As used herein, the phrase “coronary sinus region” refers to thevasculature of the left ventricle, including any portion of the coronarysinus, great cardiac vein, left marginal vein, left posteriorventricular vein, middle cardiac vein, and/or small cardiac vein or anyother cardiac vein accessible by the coronary sinus.

Accordingly, an exemplary coronary sinus lead 106 is designed to receiveatrial and ventricular cardiac signals and to deliver left ventricularpacing therapy using at least a left ventricular tip electrode 122, leftventricular ring electrode 123, left atrial pacing therapy using atleast a left atrial ring electrode 124, and shocking therapy using atleast a left atrial coil electrode 126 (or other electrode capable ofdelivering a shock). For a more complete description of a coronary sinuslead, the reader is directed to U.S. Pat. No. 5,466,254, “Coronary SinusLead with Atrial Sensing Capability” (Helland), which is incorporatedherein by reference.

Implantable device 100 is also shown in electrical communication withthe patient's heart 102 by way of an implantable right ventricular lead108 having, in this implementation, a right ventricular (RV) tipelectrode 128, a right ventricular ring electrode 130, a rightventricular coil electrode 132 (or other electrode capable of deliveringa shock), and superior vena cava (SVC) coil electrode 134 (or otherelectrode capable of delivering a shock). Typically, the rightventricular lead 108 is transvenously inserted into the heart 102 toplace the right ventricular tip electrode 128 in the right ventricularapex so that the RV coil electrode 132 will be positioned in the rightventricle and the SVC coil electrode 134 will be positioned in thesuperior vena cava. Accordingly, the right ventricular lead 108 iscapable of sensing or receiving cardiac signals, and deliveringstimulation in the form of pacing and shock therapy to the rightventricle.

Also shown in FIG. 1A is a lead 103 to which is attached a pressuresensor, not shown in FIG. 1A, but shown in FIG. 1B (which is a cutawayview of the heart 102 from a different angle than shown in FIG. 1B).Referring now to FIG. 1B, the lead 103 includes a pressure sensor 145located in the left atrium (LA). In this embodiment, the distal tip ofthe lead 103 contains the left atrial pressure sensor 145. As will bedescribed below, the implantable device 100 includes circuitry thatprocesses signals from the sensor 145 to estimate mean left atrialpressure (LAP) and/or monitor for mitral valve regurgitation (MR), inaccordance with embodiments of the present invention.

To pass the lead 103 through to the left atrium (LA), the atrial septalwall 151 may be pierced using, for example, a piercing guide wire tool(not shown), or using a lead 103 that includes on its distal end arelatively sharp and hard tip (not shown), or using a lead that includesa deployable and retractable piercing mechanism. The piercing apparatusis manipulated to create an access tunnel 154 in the septum 151. Theaccess tunnel 154 may be made in the region of the fossa ovalis sincethis may be the thinnest portion of the atrial septum 151.

The distal portion of the lead 103 is then maneuvered through the atrialseptum 151 (e.g., using the stylet) so that all or a portion of thepressure sensor 145 at the distal end of the lead 103 protrudes into theleft atrium. In this way, the sensor 145 may be used to accuratelymeasure pressure in the left atrium. If desired, the lead 103 also mayinclude another pressure sensor (not shown) positioned proximally on thelead from the sensor 145, to thereby measure pressure in the rightatrium (RA).

The lead 103 can include an attachment structure that serves to attachthe lead 103 to the septum 151. The attachment structure may take manyforms including, without limitation, one or more tines, flexiblemembranes, inflatable membranes, circumferential tines and/or J-leads.FIG. 1B represents the attachment structure in a generalized manner.

In the embodiment of FIG. 1B, the attachment structure includes a firstattachment structure 153 and a second attachment structure 157 implantedon opposite sides of the septum 151. In other applications a singleattachment structure may be implanted on one of the sides of the septum151.

In accordance with an embodiment, the first attachment structure 153 isattached to the distal portion of the lead 103. After the firstattachment structure 153 is pushed through an access tunnel 154 piercedthrough the septum 151, it expands outwardly from the lead 103 such thatit tends to prevent the distal end of the lead 103 from being pulledback through the access tunnel 154. The first attachment structure 153is then positioned against a septal wall 155 in the left atrium.

The second attachment structure 157 extends outwardly from the lead 103to help prevent the lead 103 from sliding further down into the leftatrium. As FIG. 1B illustrates, the second attachment structure 157 ispositioned against a septal wall 159 in the right atrium.

In some embodiments the attachment structures 153 and 157 are positioneda pre-defined distance apart on the lead 103. For example, the lead maybe constructed so that the spacing between the attachment structures 153and 157 is approximately equal to the thickness of the septum 151 in thearea of the access tunnel 154. In some embodiments the attachmentstructures are retractable to facilitate subsequent lead extraction.

In some embodiments, one or more of the attachment structures 153 and157 are attached to the lead 103 in a manner that enables the positionof the attachment structure to be adjusted. For example, one or both ofthe attachment structures 153 and 157 may be slideably mounted to thelead 103 so that they may be moved toward one another to firmly placeeach attachment structure against the septum 151. Such movement of theattachment structures 153 and 157 may be accomplished, for example, by amanual operation (e.g., via a tensile member such as a stylet or asheath) or automatically through the use of a biasing member (e.g., aspring).

The attachment structures are preferably configured so that they have arelatively low profile against the septal wall 151. In this way,problems associated with protruding objects in the side of the heart maybe avoided. For example, it is possible that blood clots may form on anobject that protrudes from a wall of the heart. If these blood clotsbreak loose in the left side of the heart the blood clots may travel toother areas of the body such as the brain and cause a blockage in ablood vessel (i.e., an embolism). By configuring the attachment(s) tohave a low profile, a biological layer of endothelial cells (“theintima”) may quickly build up over the attachment structure. As aresult, the likelihood of blood clots breaking loose may besignificantly reduced. The buildup of the intima also may assist infirmly attaching the attachment structure(s) 153 and/or 157 to theseptal wall 151. As a result, the lead 103 may be attached to the heartin a sufficiently stable manner so as to prevent injury to the heart andprovide accurate pressure measurements.

Various control apparatus may be attached to the proximal end of thelead 103. For example, mechanisms may be provided for moving stylets orguide wires, movable sheaths or other components (not shown) in the lead103 or for controlling the flow of fluid through lumens in the lead 103.In some applications, the control apparatus may be removed from the lead103 when the device 100 (not shown in FIG. 1B) attached to proximal endof the lead is implanted in the patient.

In other embodiments, the pressure sensor 145 can be attached to one ofthe same leads that is used for measuring electrical activity and/ordelivering electrical stimulation to the left atrium of the heart. Forexample, the left atrial pressure sensor 145 can be connected to theportion of the coronary sinus lead 106 (shown in FIG. 1A) that islocated in the left atrium.

The pressure sensor 145 can be an analog device that produces an analogsignal, or a digital device that produces a digital signal. An exampleof an ultra small digital pressure sensor is the SM5201 from SiliconMicrostructures Incorporated (SMI) in Milpitas, Calif. An example of anultra small analog pressure sensor is the SM5112 from SiliconMicrostructures Incorporated (SMI) in Milpitas, Calif. It is alsopossible that a hollow lumen catheter can be inserted within the leftatrium, with the hollow lumen catheter being in communication with apressure transducer located within the housing of the implantable device100. In such an embodiment, it will still be stated that the pressuresensor is located within a chamber of the heart since the hollow lumencan be considered part of the sensor. These are just a few examples,which are not meant to be limiting. Other pressure sensors can be used.

The lead 103 can include a lead body that may house one or moreelectrical conductors, fluid-carrying lumens and/or other components(not shown). For example, the lead 103 to which the pressure sensor 145is attached may include three conductors, one for providing anexcitation voltage required to power the sensor 145, one for ground, oneto carry the analog or digital pressure signal produced by the sensor145.

The lead 103 could be connected to a device header with, e.g., an IS-1or IS-4 connector assembly. The implanted device could then process theleft atrial pressure signal and make various calculations based from thesignal provided.

It is noted that measurements made by the implanted pressure sensor 145may be affected by changes in ambient pressure that result, e.g., fromchanges in weather and/or altitude. For a more specific example, when aperson having the implanted pressure sensor 145 drives up a mountain, orascends in an airplane, measurements from the implanted pressure sensor145 may indicate an decrease in pressure. Such confounding factors mayaffect the ability of the implanted system to estimate mean LAP, sincethe measured change in pressure is not due to physiologic changes. Oneway to overcome this problem is for the person to carry an externaldevice that monitors ambient pressure, which can be used tocalibrate/adjust the endocardial pressure measurements. For example, theexternal device (not shown) can wirelessly transmit the ambient pressuremeasurements to the implanted system 100, which can then appropriatelycalibrate/adjust the endocardial pressure measurements. In anotherembodiment, there is calibration pressure sensor located within orattached to the implantable device or within another chamber of theheart, which is used to calibrate/adjust pressure measurements fromsensor 145.

While specific techniques for implanting pressure sensors have beendescribed above, this was merely for completeness. Embodiments of thepresent invention can be used with all techniques for placement ofpressure sensors.

Through the use of the above described lead and sensor, and, in somecases, other leads and sensors implanted in the patient, the implantablecardiac device 100 can be used to estimate mean LAP and/or monitor forMR, in accordance with embodiments of the present invention, as will bedescribed below. However, before going into more details about howembodiments of the present invention estimate mean LAP and/or monitorfor MR, additional details of the exemplary implantable device 100 willbe discussed in conjunction with FIG. 2.

FIG. 2 shows a simplified block diagram depicting various components ofthe exemplary implantable device 100. The implantable device 100, asshown, can be capable of treating both fast and slow arrhythmias withstimulation therapy, including cardioversion, defibrillation, and pacingstimulation. While a particular multi-chamber device is shown, it is tobe appreciated and understood that this is done for illustrationpurposes only. Thus, the techniques and methods described below can beimplemented in connection with any suitably configured or configurableimplantable device. Accordingly, one of skill in the art could readilyduplicate, eliminate, or disable the appropriate circuitry in anydesired combination.

A housing 200 for the implantable device 100 is often referred to as the“can”, “case” or “case electrode”, and may be programmably selected toact as the return electrode for all “unipolar” modes. The housing 200may further be used as a return electrode alone or in combination withone or more of the coil electrodes 126, 132 and 134 for shockingpurposes. The housing 200 further includes a connector (not shown)having a plurality of terminals 202, 204, 206, 208, 212, 214, 216, and218 (shown schematically and, for convenience, the names of theelectrodes to which they are connected are shown next to the terminals).

To achieve right atrial sensing and pacing, the connector includes atleast a right atrial tip terminal (AR TIP) 202 adapted for connection tothe atrial tip electrode 120. A right atrial ring terminal (AR RING) 203may also be included adapted for connection to the atrial ring electrode121. To achieve left chamber sensing, pacing, and shocking, theconnector includes at least a left ventricular tip terminal (VL TIP)204, left ventricular ring terminal (VL RING) 205, a left atrial ringterminal (AL RING) 206, and a left atrial shocking terminal (AL COIL)208, which are adapted for connection to the left ventricular tipelectrode 122, the left atrial ring electrode 124, and the left atrialcoil electrode 126, respectively.

To support right chamber sensing, pacing, and shocking, the connectorfurther includes a right ventricular tip terminal (VR TIP) 212, a rightventricular ring terminal (VR RING) 214, a right ventricular shockingterminal (RV COIL) 216, and a superior vena cava shocking terminal (SVCCOIL) 218, which are adapted for connection to the right ventricular tipelectrode 128, right ventricular ring electrode 130, the RV coilelectrode 132, and the SVC coil electrode 134, respectively.

At the core of the implantable device 100 is a programmablemicrocontroller 220 that controls the various modes of stimulationtherapy. As is well known in the art, microcontroller 220 typicallyincludes one or more microprocessors, or equivalent control circuitry,designed specifically for controlling the delivery of stimulationtherapy, and may further include RAM or ROM memory, logic and timingcircuitry, state machine circuitry, and/or I/O circuitry. Typically,microcontroller 220 includes the ability to process and/or monitor inputsignals (data or information) as controlled by a program code stored ina designated block of memory (e.g., memory 260). The type ofmicrocontroller is not critical to the described implementations.Rather, any suitable microcontroller 220 may be used that carries outthe functions described herein. The use of microprocessor-based controlcircuits for performing timing and data analysis functions are wellknown in the art.

Representative types of control circuitry that may be used in connectionwith the described embodiments can include the microprocessor-basedcontrol system of U.S. Pat. No. 4,940,052 (Mann et al.), thestate-machine of U.S. Pat. Nos. 4,712,555 (Thornander et al.) and4,944,298 (Sholder), all of which are incorporated by reference herein.For a more detailed description of the various timing intervals usedwithin the implantable device and their inter-relationship, see U.S.Pat. No. 4,788,980 (Mann et al.), also incorporated herein by reference.

FIG. 2 also shows an atrial pulse generator 222 and a ventricular pulsegenerator 224 that generate pacing stimulation pulses for delivery bythe right atrial lead 104, the coronary sinus lead 106, and/or the rightventricular lead 108 via an electrode configuration switch 226. It isunderstood that in order to provide stimulation therapy in each of thefour chambers of the heart, the atrial and ventricular pulse generators,222 and 224, may include dedicated, independent pulse generators,multiplexed pulse generators, or shared pulse generators. The pulsegenerators 222 and 224 are controlled by the microcontroller 220 viaappropriate control signals 228 and 230, respectively, to trigger orinhibit the stimulation pulses.

Microcontroller 220 can also include timing control circuitry 232 tocontrol the timing of the stimulation pulses (e.g., pacing rate,atrio-ventricular (AV) delay, atrial interconduction (A-A) delay, orventricular interconduction (V-V) delay, etc.) as well as to keep trackof the timing of refractory periods, blanking intervals, noise detectionwindows, evoked response windows, alert intervals, marker channeltiming, etc., which is well known in the art.

Microcontroller 220 further includes an arrhythmia detector 234, amorphology detector 236, and optionally an orthostatic compensator and aminute ventilation (MV) response module, the latter two are not shown inFIG. 2. These components can be utilized by the implantable device 100for determining desirable times to administer various therapies,including those to reduce the effects of orthostatic hypotension. Theaforementioned components may be implemented in hardware as part of themicrocontroller 220, or as software/firmware instructions programmedinto the device and executed on the microcontroller 220 during certainmodes of operation.

The electronic configuration switch 226 includes a plurality of switchesfor connecting the desired electrodes to the appropriate I/O circuits,thereby providing complete electrode programmability. Accordingly,switch 226, in response to a control signal 242 from the microcontroller220, determines the polarity of the stimulation pulses (e.g., unipolar,bipolar, combipolar, etc.) by selectively closing the appropriatecombination of switches (not shown) as is known in the art.

Atrial sensing circuits 244 and ventricular sensing circuits 246 mayalso be selectively coupled to the right atrial lead 104, coronary sinuslead 106, and the right ventricular lead 108, through the switch 226 fordetecting the presence of cardiac activity in each of the four chambersof the heart. Accordingly, the atrial (ATR. SENSE) and ventricular (VTR.SENSE) sensing circuits, 244 and 246, may include dedicated senseamplifiers, multiplexed amplifiers, or shared amplifiers. Switch 226determines the “sensing polarity” of the cardiac signal by selectivelyclosing the appropriate switches, as is also known in the art. In thisway, the clinician may program the sensing polarity independent of thestimulation polarity. The sensing circuits (e.g., 244 and 246) areoptionally capable of obtaining information indicative of tissuecapture.

Each sensing circuit 244 and 246 preferably employs one or more lowpower, precision amplifiers with programmable gain and/or automatic gaincontrol, bandpass filtering, and a threshold detection circuit, as knownin the art, to selectively sense the cardiac signal of interest. Theautomatic gain control enables the device 100 to deal effectively withthe difficult problem of sensing the low amplitude signalcharacteristics of atrial or ventricular fibrillation.

The outputs of the atrial and ventricular sensing circuits 244 and 246are connected to the microcontroller 220, which, in turn, is able totrigger or inhibit the atrial and ventricular pulse generators 222 and224, respectively, in a demand fashion in response to the absence orpresence of cardiac activity in the appropriate chambers of the heart.Furthermore, the microcontroller 220 is also capable of analyzinginformation output from the sensing circuits 244 and 246 and/or the dataacquisition system 252 to determine or detect whether and to what degreetissue capture has occurred and to program a pulse, or pulses, inresponse to such determinations. The sensing circuits 244 and 246, inturn, receive control signals over signal lines 248 and 250 from themicrocontroller 220 for purposes of controlling the gain, threshold,polarization charge removal circuitry (not shown), and the timing of anyblocking circuitry (not shown) coupled to the inputs of the sensingcircuits, 244 and 246, as is known in the art.

For arrhythmia detection, the device 100 utilizes the atrial andventricular sensing circuits, 244 and 246, to sense cardiac signals todetermine whether a rhythm is physiologic or pathologic. In reference toarrhythmias, as used herein, “sensing” is reserved for the noting of anelectrical signal or obtaining data (information), and “detection” isthe processing (analysis) of these sensed signals and noting thepresence of an arrhythmia. The timing intervals between sensed events(e.g., P-waves, R-waves, and depolarization signals associated withfibrillation which are sometimes referred to as “F-waves” or“Fib-waves”) are then classified by the arrhythmia detector 234 of themicrocontroller 220 by comparing them to a predefined rate zone limit(i.e., bradycardia, normal, low rate VT, high rate VT, and fibrillationrate zones) and various other characteristics (e.g., sudden onset,stability, physiologic sensors, and morphology, etc.) in order todetermine the type of remedial therapy that is needed (e.g., bradycardiapacing, anti-tachycardia pacing, cardioversion shocks or defibrillationshocks, collectively referred to as “tiered therapy”).

Cardiac signals are also applied to inputs of an analog-to-digital (A/D)data acquisition system 252. The data acquisition system 252 isconfigured (e.g., via signal line 251) to acquire intracardiacelectrogram (“IEGM”) signals, convert the raw analog data into a digitalsignal, and can store the digital signals for later processing and/ortelemetric transmission to an external device 254. The data acquisitionsystem 252 can be coupled to the right atrial lead 104, the coronarysinus lead 106, and the right ventricular lead 108 through the switch226 to sample cardiac signals across any pair of desired electrodes.

The microcontroller 220 is further coupled to a memory 260 by a suitabledata/address bus 262, wherein the programmable operating parameters usedby the microcontroller 220 are stored and modified, as required, inorder to customize the operation of the implantable device 100 to suitthe needs of a particular patient. Such operating parameters define, forexample, pacing pulse amplitude, pulse duration, electrode polarity,rate, sensitivity, automatic features, arrhythmia detection criteria,and the amplitude, waveshape and vector of each shocking pulse to bedelivered to the patient's heart 102 within each respective tier oftherapy. One feature of the described embodiments is the ability tosense and store a relatively large amount of data (e.g., from the dataacquisition system 252), which data may then be used for subsequentanalysis to guide the programming of the device. The memory 260 can alsostore the pressure data related to embodiments of the present invention.

The operating parameters of the implantable device 100 may benon-invasively programmed into the memory 260 through a telemetrycircuit 264 in telemetric communication via communication link 266 withthe external device 254, such as a programmer, transtelephonictransceiver, or a diagnostic system analyzer. The microcontroller 220activates the telemetry circuit 264 with a control signal 268. Thetelemetry circuit 264 advantageously allows intracardiac electrogramsand status information relating to the operation of the device 100 (ascontained in the microcontroller 220 or memory 260) to be sent to theexternal device 254 through an established communication link 266.

The implantable device 100 can further include a physiologic sensor 270,commonly referred to as a “rate-responsive” sensor because it istypically used to adjust pacing stimulation rate according to theexercise state of the patient. However, the physiological sensor 270 mayfurther be used to detect changes in cardiac output, changes in thephysiological condition of the heart, or diurnal changes in activity(e.g., detecting sleep and wake states). Accordingly, themicrocontroller 220 responds by adjusting the various pacing parameters(such as rate, AV Delay, V-V Delay, etc.) at which the atrial andventricular pulse generators, 222 and 224, generate stimulation pulses.While shown as being included within the implantable device 100, it isto be understood that the physiologic sensor 270 may also be external tothe implantable device 100, yet still be implanted within or carried bythe patient. Examples of physiologic sensors that may be implemented indevice 100 include known sensors that, for example, sense respirationrate, pH of blood, ventricular gradient, oxygen saturation, bloodpressure and so forth. Another sensor that may be used is one thatdetects activity variance, wherein an activity sensor is monitoreddiurnally to detect the low variance in the measurement corresponding tothe sleep state. For a more detailed description of an activity variancesensor, the reader is directed to U.S. Pat. No. 5,476,483 (Bornzin etal.), which is hereby incorporated by reference.

The implantable device 100 additionally includes a battery 276 thatprovides operating power to all of the circuits shown in FIG. 2. For adevice that employs shocking therapy, the battery 276 should be capableof operating at low current drains for long periods of time (e.g.,preferably less than 10 μA), and be capable of providing high-currentpulses (for capacitor charging) when the patient requires a shock pulse(e.g., preferably, in excess of 2 A, at voltages above 200 V, forperiods of 10 seconds or more). The battery 276 also desirably has apredictable discharge characteristic so that elective replacement timecan be detected.

The implantable device 100 can further include magnet detectioncircuitry (not shown), coupled to the microcontroller 220, to detectwhen a magnet is placed over the implantable device 100. A magnet may beused by a clinician to perform various test functions of the implantabledevice 100 and/or to signal the microcontroller 220 that the externalprogrammer 254 is in place to receive or transmit data to themicrocontroller 220 through the telemetry circuits 264.

The exemplary implantable device 100 is also shown as including animpedance measuring circuit 278 that is enabled by the microcontroller220 via a control signal 280. The known uses for an impedance measuringcircuit 278 include, but are not limited to, lead impedance surveillanceduring the acute and chronic phases for proper performance; leadpositioning or dislodgement; detecting operable electrodes andautomatically switching to an operable pair if dislodgement occurs;measuring respiration or minute ventilation; measuring thoracicimpedance for determining shock thresholds; detecting when the devicehas been implanted; measuring stroke volume; and detecting the openingof heart valves, etc. The impedance measuring circuit 278 isadvantageously coupled to the switch 226 so that any desired electrodemay be used.

In the case where the implantable device 100 is intended to operate asan implantable cardioverter/defibrillator device, it detects theoccurrence of an arrhythmia, and automatically applies an appropriatetherapy to the heart aimed at terminating the detected arrhythmia. Tothis end, the microcontroller 220 further controls a shocking circuit282 by way of a control signal 284. The shocking circuit 282 generatesshocking pulses of low (e.g., up to 0.5 J to 2.0 J), moderate (e.g., 2.5J to 10 J), or high energy (e.g., 11 J to 40 J), as controlled by themicrocontroller 220. Such shocking pulses are applied to the patient'sheart 102 through at least two shocking electrodes, and as shown in thisembodiment, selected from the left atrial coil electrode 126, the RVcoil electrode 132, and/or the SVC coil electrode 134. As noted above,the housing 200 may act as an active electrode in combination with theRV electrode 132, and/or as part of a split electrical vector using theSVC coil electrode 134 or the left atrial coil electrode 126 (i.e.,using the RV electrode as a common electrode).

Cardioversion level shocks are generally considered to be of low tomoderate energy level (so as to minimize pain felt by the patient),and/or synchronized with an R-wave and/or pertaining to the treatment oftachycardia. Defibrillation shocks are generally of moderate to highenergy level (i.e., corresponding to thresholds in the range of 5 J to40 J), delivered asynchronously (since R-waves may be too disorganized),and pertaining exclusively to the treatment of fibrillation.Accordingly, the microcontroller 220 is capable of controlling thesynchronous or asynchronous delivery of the shocking pulses.

A typical pressure sensor generates electrical signals indicative ofchanges in a sensed pressure. Thus, one or more wires may be used toconnect the sensor 145 to the device 100, as was described above. FIG. 2illustrates an embodiment where a pressure signal P1 (e.g., from sensor145) is received by the device 100 via terminal 211. Ananalog-to-digital (ND) data acquisition system 253 may be configured(e.g., via signal line 255) to acquire and amplify the signal P1,convert the raw analog data into a digital signal, filter the signal andstore the digital signal (e.g., in memory 260) for later processing by,for example, a mean LAP processing component 238, a MR monitoringcomponent 239 and/or telemetric transmission to an external device 254.As mentioned above, it is also possible that the pressure sensor canproduce a digital signal. In such a case, the ND 253 would not beneeded. In addition to (or instead of) storing the pressure signals, itis also possible that the pressure signals be processing in real or nearreal time.

The implanted device 100 is also shown as including a patient alert 221,which can inform the patient that medical attention should be sought. Inaccordance with an embodiment, the alert 221 is provided through anelectromechanical transducer that generates sound and/or mechanicalvibration, that can be heard and/or felt by the patient. These are justa few examples of patient alerts, which are not meant to be limiting.One of ordinary skill in the art will appreciate that other types ofpatient alerts can be used, while still being within the spirit andscope of the present invention.

The implantable device may also includes a drug pump 261, controlled bythe microcontroller 220, to compensate, if necessary, for drug efficacyproblems. For example, if an initial dosage of a drug for treating CHFis not adequately effective, the drug pump may be controlled to increasethe dosage.

Now that exemplary details of the implantable device 100 have beenprovided, additional details of the various embodiments of the presentinvention will be provided.

FIG. 3A illustrates a portion of an exemplary EGM signal, and FIG. 3Billustrates an exemplary corresponding pressure signal representative ofpressure within the left atrium of a patient's heart. The signal of FIG.3A can be obtained, e.g., by the implantable device 100, or a similarimplantable device. The signal of FIG. 3B can be obtained, e.g., usingthe pressure sensor 145 that is attached by lead 103 to the implantabledevice 100.

Referring to FIG. 3A, each cycle of the EGM waveform, which correspondsto a heart beat, includes a P-wave that is a normally small positivewave caused by the beginning of a heart beat and representing atrialdepolarization (also known as atrial activation), which initiatescontraction of the atrial musculature. Following the P-wave there is aportion which is substantially constant in amplitude. The R-wave(representing ventricular depolarization, also known as ventricularactivation) of the EGM is a rapid positive deflection that occurs afterthe substantially constant portion.

Referring to FIG. 3B, each cycle of the left atrial pressure waveformincludes an a-wave, which is produced by an atrial contraction.Following the a-wave is a c-wave, which is produced by the leftventricle contracting against the closed mitral valve (MV). Followingthe c-wave is a v-wave, which is produced by the left ventricle endsystole between the aortic valve closure and the mitral valve opening.Also shown in FIG. 3B are windows 302 and 304, which are discussed inmore detail below during the discussion of FIG. 4. A vertical line 320is representative of the relative timing of an R-wave, as detected froma corresponding EGM signal (e.g., as shown in FIG. 3A). Also shown arehorizontal lines 322, 324 and 326, which are discussed in more detailbelow during the discussion of FIG. 4.

Additional details of specific embodiments of the present invention willnow be described with reference to the high level flow diagrams of FIGS.4-6. During discussion of these flow diagram, frequent reference will bemade back to the waveform of FIG. 3B. Reference will also be made toFIG. 3C, which is another left atrial pressure waveform.

Estimating Mean LAP

FIG. 4 will now be used to describe how mean LAP can be estimated, inaccording with embodiments of the present invention. Referring to FIG.4, at a step 402 an EGM signal and a corresponding pressure signal areobtained. The EGM signal is representative of electrical functioning ofthe patient's heart during a plurality of cardiac cycles, and thecorresponding pressure signal is representative of pressure within theleft atrium the patient's heart during the cardiac cycles.

At a step 404, for each of a plurality of cardiac cycles represented inthe pressure signal there is a determination of an average (i.e., mean)of a window of the pressure signal. In accordance with specificembodiments, the start of the window is defined relative to an eventdetected in the EGM signal that corresponds to the pressure signal. Inaccordance with specific embodiments, the window is defined relative toa ventricular activation that is detected in the EGM signal. Forexample, referring to FIG. 3B, the vertical line 320 shows the timing ofan R-wave, as detected from the EGM signal (of FIG. 3A) that correspondsto the pressure signal of FIG. 3B. Also shown in FIG. 3B is an exemplarywindow 302 that is defined relative to the R-wave represented by line320. As was explained above, the R-wave is representative of anintrinsic ventricular activation. It is also possible that theventricular activation is a paced V-pulse, instead of an intrinsicR-wave.

In this example, the start of the window 302 coincides with theventricular activation, as detected based on a detected R-wave orV-pulse. However, this is not necessary. For example, the window maystart a fixed delay after an R-wave or V-pulse. It is also possible thatthe window can be defined relative to an atrial activation (representedby a P-wave). Namely, if a device senses off the P-wave and knows the PRinterval or AV delay, or has a good estimation of that value, the windowcan start a specified delay after a P-wave.

The length of each window (e.g., 302) is defined to include at least oneof an a-wave and a c-wave, but not a v-wave, of the cardiac cyclerepresented in the pressure signal. Preferably, the length of the windowis defined to include both the a-wave and the c-wave, as is the casewith exemplary window 302 shown in FIG. 3B. In accordance with variousembodiments, each window length may be a percentage of the previous orupcoming cardiac cycle length (e.g. 30%), or a percentage of the mean ofa previous plurality of cardiac cycle lengths (e.g. 30% of the mean ofthe previous 8 RR intervals), or the length may be a fixed value (e.g.120 ms). Mechanistically, the window preferably corresponds to the timeafter ventricular depolarization (i.e., activation) to the time ofventricular contraction and mitral valve closure. In terms of the LAPcharacteristics, this includes the “a-wave” and “c-wave” portions, asmentioned above.

Referring again to FIG. 4, at a step 406, the mean left atrial pressure(LAP) is estimated based on the averages determined at step 404. Forexample, each average determined for a cardiac cycle at step 404 can beused as a separate estimate of mean LAP. Alternatively, at step 406 anaverage can be determined of a plurality of the averages determined atstep 404, and the average of the plurality of averages can be used asthe estimate of mean LAP. In an alternative embodiment, at step 406there is a determination of a median of a plurality of averagesdetermined at step 404, and the median of the plurality of averages isused as the estimate of mean LAP.

An advantage of the embodiments described with reference to FIG. 4 isthat they avoid the confounding effects of MR and conduction aberranceswhich result in large “v-waves” that occur in the LAP waveform late inthe cardiac cycle. In other words, a large v-wave that may occur due toMR (as shown in FIG. 3C) will not corrupt the estimates of mean LAP,since the embodiments described above purposefully avoid measures of thev-wave when estimating mean LAP.

A response can be triggered when the estimated mean LAP exceeds a firstthreshold, or drops below a second threshold. Changes in mean LAP canalso be monitored by repeatedly (e.g., continually, or from time totime) performing the steps discussed with reference to FIG. 4. In thismanner, trends in the mean LAP of the patient can be monitored.Additionally, a response can be triggered if the change in mean LAP,within a specified amount of time, that exceeds a correspondingthreshold.

Referring back to FIG. 2, the patient alert 221 can be used to inform apatient when their mean LAP exceeds a threshold or drops below athreshold. The device 100 can alternatively use the telemetry circuit toinform a physician, clinician and/or any other person (or processor) ofthe same. The patient alert 221 can include an indicator that provides,for example, an acoustic, mechanical vibration, optical and/orelectrical indication and/or stimulation. Triggering of an alert canindicate to a patient, physician, clinician, monitoring staff, and/ormonitoring computer, e.g., that a change in mean LAP that is indicativeof a heart failure exacerbation (also known as, an episode of acuteheart failure) is developing. The patient can be instructed to call hisphysician when the patient alert is triggered, and/or the patient can beinstructed to take a specific drug (e.g., a diuretic) when the patientalert is triggered. It is also possible that the implantable deviceincludes a drug pump (e.g., 261) that will deliver an appropriate dosageof a drug (e.g., a diuretic) in response to one or more of theconditions mentioned above (e.g., estimated mean LAP exceeds a firstthreshold, or drops below a second threshold). In accordance with anembodiment of the present invention, mean LAP information can be stored.This can include, for example, storing mean LAP estimates (which can bedisplayed with previously determined mean LAP estimates, from a monthago, and compared to see improvement or worsening CHF condition). Suchinformation can be continually, or from time to time, automaticallyuploaded to an external device (e.g., 254). Such an external monitoringdevice can be located, e.g., in the patients' home, and the informationcan be transmitted (e.g., through telephone lines or the Internet) to amedical facility where a physician can analyze the information.Alternatively, the external device can be located at a medical facility,and the information can be uploaded when the patient visits thefacility.

A threshold can be predetermined. Alternatively, a threshold can bedynamic in that its value is determined based on previously measuredand/or calculated values. A common threshold can be used for manypatients. Alternatively, thresholds can be patient specific.

Monitoring for Mitral Valve Regurgitation (MR)

FIG. 5 will now be used to describe how to monitor for MR, in accordingwith embodiments of the present invention. Referring to FIG. 5, at astep 502, which is similar to step 402, an EGM signal and acorresponding pressure signal are obtained. The EGM signal isrepresentative of electrical functioning of the patient's heart during aplurality of cardiac cycles, and the corresponding pressure signal isrepresentative of pressure within the left atrium the patient's heartduring the cardiac cycles.

At a step 504, for each of a plurality of cardiac cycles represented inthe EGM and pressure signals, there is a determination of a maximum peakwithin a first window of the pressure signal, and a determination of amaximum peak within a second window of the pressure signal. The firstwindow is defined to include at least one of an a-wave and a c-wave, butnot a v-wave, of the cardiac cycle represented in the pressure signal.The second window is defined to include the v-wave of the cardiac cyclerepresented in the pressure signal. For the embodiments described withreference to FIG. 5, it is preferred that the second window includesneither the a-wave or the c-wave.

In accordance with specific embodiments, the start of the first windowis defined relative to an event detected in the EGM signal, in any ofthe manners as was discussed above with regards to step 404 of FIG. 4.Referring to FIG. 3B, the window 302 is an example of such a firstwindow. The start of the second window can be defined relative to anevent in the EGM, or relative to the first window. Referring to FIG. 3B,the window 304 is an example of such a second window. The second window304 can be defined as starting at the end of the first window, e.g., asshown in FIG. 3B. Alternatively, the second window 304 can be defined asstarting a specified delay after a ventricular or atrial activation. Forexample, the second window can be defined to start 120 msec after aventricular activation. It is also possible that there can be a smalltime gap between the first and second windows, or a small overlapbetween first and second windows, although such gap or overlap is notpreferred.

The length of each second window may be a percentage of the previous orupcoming cardiac cycle length (e.g. 70%), or a percentage of the mean ofa previous plurality of cardiac cycle lengths (e.g. 70% of the mean ofthe previous 8 RR or W intervals), or the length may be a fixed value(e.g. 280 ms). It may also be that the length of the second window isthe remainder of a cycle length not included in the first window.Mechanistically, the second window preferably corresponds to the timeafter ventricular contraction and mitral valve closure to the time ofthe next ventricular activation.

Referring again to FIG. 5, at a step 506 the maximum peak detectedwithin one or more first window is compared to a maximum peak detectedwithin one or more second window. For example, the peaks of the firstand second windows for each cardiac cycle can be compared to one anotherat step 506. Alternatively, at step 506 an average (or median) can bedetermined of a plurality of first window peaks determined at step 504,and an average (or median) can be determined of a plurality of secondwindow peaks determined at step 504, and then the average (or median)first window peak can be compared to the average (or median) secondwindow peak.

Still referring to FIG. 5, at a step 508, MR is monitored for based onresults of the comparison(s) performed at step 506. Reference back toFIG. 3B shows that the peak 314 within the second window 302 is aboutthe same as the peak 312 within the first window 302. This is indicativeof an absence of MR. In contrast, FIG. 3C shows that the peak 314′within the second window 304 is much greater than the peak 312′ withinthe first window 302, which is indicative of the presence of MR.

Step 508 can be accomplished in a variety of manners. For example, step508 can include determining a ratio based on the maximum peak detectedwithin one or more first window to the maximum peak detected within oneor more said second window, (or vice versa), and detecting MR when theratio falls below (or exceeds) a corresponding threshold. Alternatively,step 508 can include determining a difference between the maximum peakdetected within one or more first window and the maximum peak detectedwithin one or more second window, and detecting MR when the differenceexceeds a corresponding threshold.

FIG. 6 will now be used to describe how to monitor for MR, in accordingwith other embodiments of the present invention. Referring to FIG. 6, ata step 602, which is similar to steps 402 and 502, an EGM signal and acorresponding pressure signal are obtained, where the EGM signal isrepresentative of electrical functioning of the patient's heart during aplurality of cardiac cycles, and the corresponding pressure signal isrepresentative of pressure within the left atrium the patient's heartduring the cardiac cycles.

At a step 604, for each of a plurality of cardiac cycles represented inthe EGM and pressure signals, there is a determination of an average ofa first window of the pressure signal, and a determination of an averageof a second window of the pressure signal. The first window is definedto include at least one of an a-wave and a c-wave, but not a v-wave, ofthe cardiac cycle represented in the pressure signal. The second windowis defined to include the v-wave of the cardiac cycle represented in thepressure signal. The start and length of the first window can be definedin the same manners that the first window can be defined with referenceto step 504.

In the embodiments discussed with reference to FIG. 6, the start of thesecond window can be defined relative to an event in the EGM, orrelative to the first window. Referring to FIG. 3B, the window 304 is anexample of such a second window. The second window 304 can be defined asstarting at the end of the first window. Alternatively, the secondwindow 304 can be defined as starting a specified delay after aventricular or atrial activation. For example, the second window can bedefined to start 120 msec after a ventricular activation. It is alsopossible that there is a small time gap between the first and secondwindows, or a small overlap between the first and second windows. Inthis embodiments discussed with reference to FIG. 6 is also possiblethat the second window encompass an entire cardiac cycle (e.g., RR or VVinterval), and thus that the second window completely encompasses thefirst window. For example, it is possible that the second window startswhere the first window starts, but that the second window is longer thanthe first window so that the second window will include the v-wave.

At a step 606, one or more average determined for a first window iscompared to one or more average determined for a second window. Forexample, the average of the first window and the average of the secondwindow for each cardiac cycle can be compared to one another at step606. Alternatively, at step 606 an average (or median) can be determinedof a plurality of first window averages determined at step 604, and anaverage (or median) can be determined of a plurality of second windowaverages determined at step 404, and then the average (or median) firstwindow average can be compared to the average (or median) second windowaverage. It is noted that where the length of the second window is equalto an entire cardiac cycle, the average determined for the second windowis an average of an entire cardiac interval represented in the leftatrial pressure signal.

Still referring to FIG. 6, at a step 608 MR is monitored for based onresults of the comparison(s) performed at step 606. Referring back toFIG. 3B, an exemplary first window is shown at 302, and an exemplarysecond window is shown at 304, with horizontal line 322 illustrating theaverage of the first window 302, and horizontal line 324 illustratingthe average of the second window 304. It can be appreciated that theaverage 324 of the second window 304 is about the same as the average322 of the first window 302. This is indicative of an absence of MR. Incontrast, referring to FIG. 3C, it can be appreciated that the average324′ of the second window 304 is significantly greater than the average322′ of the first window 302, which is indicative of the presence of MR.

As mentioned above, it is also possible that the length of the secondwindow is equal to an entire cardiac cycle. In such a case, the averagedetermined for the second window is the average of the entire cardiacinterval represented in the left atrial pressure signal, which isillustrated by line 326 in FIG. 3B, and by line 326′ in FIG. 3C. It canbe appreciated from FIG. 3B that the average 326 of the second window(where the second window extends an entire cardiac interval) is aboutthe same as the average 322 of the first window 302, which is indicativeof an absence of MR. It can be appreciated from FIG. 3C that the average326′ of the second window (where the second window extends an entirecardiac interval) is significantly greater than the average 322′ of thefirst window 302, which is indicative of the presence of MR.

Step 608 can be accomplished in a variety of manners. For example, step608 can include determining a ratio based on the average of one or morefirst window to the average of one or more second window, (or viceversa), and detecting MR when the ratio falls below (or exceeds) acorresponding threshold. Alternatively, step 608 can include determininga difference between the average of one or more first window and theaverage of one or more second window, and detecting MR when thedifference exceeds a corresponding threshold.

One or more response can be triggered if MR is detected. In accordancewith an embodiment of the present invention, information related to eachMR can be stored. This can include, for example, storing pressure signaldata for each MR and/or providing a measure of MR burden (which can bedisplayed with previously determined MR burdens, from a month ago, andcompared to see improvement or worsening of MR condition). Suchinformation can be continually, or from time to time, automaticallyuploaded to an external device (e.g., 254). Such an external monitoringdevice can be located, e.g., in the patients' home, and the informationcan be transmitted (e.g., through telephone lines or the Internet) to amedical facility where a physician can analyze the information.Alternatively, the external device can be located at a medical facility,and the information can be uploaded when the patient visits thefacility.

In accordance with an embodiment of the present invention, MR burden canbe monitored by determining a number of MRs that occur during eachpredetermined period of time (e.g., 24 hours). By tracking MR burden inthis manner, there can be a determination of whether MR burden hasincreased or decreased over time. Additionally, one or more MR burdenthreshold can be defined, so that one of the above responses can betriggered in response to a specific MR burden threshold being crossed.FIG. 7 shows an exemplary graph of MR burden over time, with dashed line702 representing an exemplary threshold.

Example embodiments of the methods, systems, and components of thepresent invention have been described herein. As noted elsewhere, theseexample embodiments have been described for illustrative purposes only,and are not limiting. Other embodiments are possible and are covered bythe invention. Such embodiments will be apparent to persons skilled inthe relevant art(s) based on the teachings contained herein.

Thus, the breadth and scope of the present invention should not belimited by any of the above-described exemplary embodiments, but shouldbe defined only in accordance with the following claims and theirequivalents.

1. In an implantable system, a method for monitoring a patient's heartfor mitral valve regurgitation (MR), comprising: (a) obtaining anelectrogram (EGM) signal and a corresponding pressure signal, the EGMsignal representative of electrical functioning of the patient's heartduring a plurality of cardiac cycles, the corresponding pressure signalrepresentative of pressure within the left atrium the patient's heartduring the cardiac cycles; (b) for each of a plurality of cardiac cyclesrepresented in the EGM and pressure signals, (b.1) determining a maximumpeak within a first window of the pressure signal, wherein a start ofthe first window is defined relative to an event detected in the EGMsignal, and wherein a length of the first window is defined to includeat least one of an a-wave and a c-wave, but not a v-wave, of the cardiaccycle represented in the pressure signal; and (b.2) determining amaximum peak within a second window of the pressure signal, wherein astart of the second window is defined relative to an event detected inthe EGM signal or relative to the first window, and wherein a length ofthe second window is defined to include the v-wave of the cardiac cyclerepresented in the pressure signal; (c) comparing the maximum peakdetected within one or more said first window to the maximum peakdetected within one or more said second window; and (d) monitoring forMR based on results of the comparing.
 2. The method of claim 1, wherein:step (c) includes determining a ratio based on the maximum peak detectedwithin one or more said first window and the maximum peak detectedwithin one or more said second window, or vice versa; and step (d)includes detecting MR by comparing the ratio to a threshold.
 3. Themethod of claim 1, wherein: step (c) includes determining a differencebetween the maximum peak detected within one or more said first windowand the maximum peak detected within one or more said second window; andstep (d) includes detecting MR when the difference exceeds a threshold.4. An implantable system for monitoring a patient's heart for mitralvalve regurgitation (MR), comprising: one or more electrode to obtain anelectrogram (EGM) signal representative of electrical functioning of thepatient's heart during a plurality of cardiac cycles; one or more sensorto obtain a corresponding pressure signal representative of pressurewithin the left atrium the patient's heart during the cardiac cycles;and one or more processor to determine, for each of a plurality ofcardiac cycles represented in the EGM and pressure signals, a maximumpeak within of a first window of the pressure signal, wherein a start ofthe first window is defined relative to an event detected in the EGMsignal, and wherein a length of the first window is defined to includeat least one of an a-wave and a c-wave, but not a v-wave, of the cardiaccycle represented in the pressure signal; and a maximum peak within asecond window of the pressure signal, wherein a start of the secondwindow is defined relative to an event detected in the EGM signal orrelative to the first window, and wherein a length of the second windowis defined to include the v-wave of the cardiac cycle represented in thepressure signal; wherein the one or more processor monitors for MR basedon comparisons of the maximum peak detected within one or more saidfirst window to the maximum peak detected within one or more said secondwindow.
 5. The system of claim 4, wherein the one or more processor:determines a ratio based on the maximum peak detected within one or moresaid first window and the maximum peak detected within one or more saidsecond window, or vice versa; and detects MR by comparing the ratio to athreshold.
 6. The system of claim 4, wherein the one or more processor:determines a difference between the maximum peak detected within one ormore said first window and the maximum peak detected within one or moresaid second window; and detects MR when the difference exceeds athreshold.